Space travel may have promising implications for innovative approaches in biomedical research. But there are potential challenges and health concerns associated with exposures from space travel that warrant the need for mechanistic studies to determine the effects on various organ systems including the cardiovascular system. Radiation exposure associated with space flight is known to adversely affect the heart and vascular system. However, less is known about the effects of microgravity on the cardiovascular system. Various functions of the cardiovascular system may be affected by microgravity. Studies have investigated changes in the cytoskeleton of various cell types in response to simulated microgravity. Other studies investigated the effect of microgravity on the permeability and migration of endothelial cells and myocardial atrophy associated with endothelial dysfunction. In addition, coagulation, vasoconstriction, blood volume, and cardiac dimensions were outcome measures of studies aimed at understanding the implications of microgravity on the cardiovascular system. This comprehensive review summarizes the effect of microgravity on various aspects of the cardiovascular system.

The expression of the myristoylated alanine-rich C-kinase substrate (MARCKS) family of proteins in the kidneys plays an important role in the regulation of the renal epithelial sodium channel (ENaC) and hence overall blood pressure regulation. The function of MARCKS is regulated by post-translational modifications including myristoylation, phosphorylation, and proteolysis. Proteases known to cleave both ENaC and MARCKS have been shown to contribute to the development of high blood pressure, or hypertension. Here, we investigated protein expression and proteolysis of MARCKS, protein expression of multiple protein kinase C (PKC) isoforms, and protein expression and activity of several different proteases in the kidneys of diabetic db/db mice compared to wild-type littermate mice. In addition, MARCKS protein expression was assessed in cultured mouse cortical collecting duct (mpkCCD) cells treated with normal glucose and high glucose concentrations. Western blot and densitometric analysis showed less abundance of the unprocessed form of MARCKS and increased expression of a proteolytically cleaved form of MARCKS in the kidneys of diabetic db/db mice compared to wild-type mice. The protein expression levels of PKC delta and PKC epsilon were increased, while cathepsin B, cathepsin S, and cathepsin D were augmented in diabetic db/db kidneys compared to those of wild-type mice. An increase in the cleaved form of MARCKS was observed in mpkCCD cells cultured in high glucose compared to normal glucose concentrations. Taken together, these results suggest that high glucose may contribute to an increase in the proteolysis of renal MARCKS, while the upregulation of the cathepsin proteolytic pathway positively correlates with increased proteolysis of MARCKS in diabetic kidneys, where PKC expression is augmented.

Amaç: Sağlık Bakanlığı’nın Koruyucu Ağız ve Diş Sağlığı Programı Muayene Takip Formunda yer alan verilerden faydalanarak ilköğretim birinci sınıf öğrencilerin ağız ve diş sağlığı durumlarını ve etkileyen faktörleri değerlendirmek amaçlanmıştır. Yöntem: Araştırmada 2017-2018 Eğitim ve Öğretim Döneminde Kayseri İl Sağlık Müdürlüğü tarafından yapılmış olan ağız ve diş sağlığı çalışmaları kapsamında taranan 13,836 öğrencinin formları değerlendirilmiştir. Formlar iki bölümden oluşmakta olup, ilk bölümde öğrenci velilerinin doldurması gereken ve öğrencilerin kişisel özellikleri, diş sağlığına yönelik tutum ve davranışları ile ilgili bilgiler bulunmaktadır. İkinci bölüm ise yapılan muayenelerin bulgularını içermektedir. Elde edilen nicel veriler ortalama ve standart sapma, nitel veriler sayı ve yüzde ile gösterilmiş, kişisel özellik ve alışkanlıkları dmft indeksi ile karşılaştırmak için bağımsız örneklerde t testi, Tek Yönlü ANOVA ve Post-hoc Tukey testleri kullanılmıştır. İstatistiksel analizlerde p<0.05 değeri anlamlı kabul edilmiştir. Bulgular: Değerlendirilen öğrencilerde çürük deneyimi prevalansı %73.3, tedavi edilmemiş çürüklü öğrenci yüzdesi %69.6 olarak bulunmuştur. Öğrencilerin dmft indeksi 3.58±3.32 olarak bulunmuştur. Öğrencilerin tarama sonuçlarına göre dmft indeksi erkeklerde, veli öğrenim durumu ortaokul ve altı olanlarda, kendine ait diş fırçası olmayanlarda, dişlerini fırçalamayanlarda, diş eti kanaması olanlarda, ortodontik tedavi görenlerde, en son diş hekimine gitme sebebi ağrı veya yakınma ve tedavi veya tedavi takibi olanlarda diğer gruplara göre istatistiksel olarak anlamlı şekilde daha yüksek bulunmuştur (p0.05). Sonuç: Kayseri’deki okullarda tarama verilerinin sonuçları çürük sıklığının Dünya Sağlık Örgütü tarafından belirlenen hedeflerin çok gerisinde olduğunu göstermektedir. Ağız-diş sağlığı ölçütlerimizi iyileştirmeye yönelik olarak “Koruyucu Diş Hekimliği Hizmetleri”nin yaygınlaştırılması gerektiği düşünülmektedir

Background: Alpha-1 antitrypsin (AAT) is a multifunctional protease inhibitor that has been shown to have anti-inflammatory properties in various diseases. AAT has been reported to protect against renal injury via anti-apoptotic, anti-fibrotic, and anti-inflammatory effects. However, its role in mitigating renal inflammation and reducing high blood pressure induced by salt-loading has never been studied. Methods: In this study, we salt-loaded 129Sv mice to induce hypertension and then administered purified human AAT (hAAT) or the vehicle to investigate whether renal inflammation and associated inflammatory/signaling pathways are mitigated. Results: Western blotting and densitometric analysis showed administration of hAAT attenuated protein expression of kidney injury molecule-1 (KIM1), CD93, CD36, and the toll-like receptor 2 and 4 (TLR-2/4) in kidney lysates. Similarly, protein expression of two key inflammatory transcription factors, signal transducer and activator of transcription 3 (STAT3) and NF-Kappa B were shown to be attenuated in the kidneys of 129Sv mice that received hAAT. Conversely, hAAT treatment upregulated the expression of heat shock protein 70 (HSP70) and immunohistochemistry confirmed these findings. Conclusions: Purified hAAT administration may be efficacious in mitigating renal inflammation associated with the development of hypertension from salt-loading, potentially through a mechanism involving the reduction of pro-inflammatory and injury-associated proteins.

Our prior studies have shown that B type Natriuretic Peptide (BNP) decreases absorption from the gastrointestinal (GI) tract. Since non-muscle myosin-type II (NMM-II) is known to have a role in epithelial tight junction regulation, we aimed to test whether BNP has an effect on the localization and expression of NMM-II in the intestinal villi. We treated wild type mice with a 10 ng/g intravenous bolus of BNP followed by infusion of BNP at 1ng/g/minute vs. vehicle control. The mice were then euthanized and intestinal tissue isolated and sectioned. The tissue was immune-stained for NMM-II and examined using fluorescence microscopy. The tissue section not treated with antibody to NMM-II was used as a methodological control to evaluate the non-specific binding. Scanning electron micrographic images were taken to compare structural differences between the two groups. Western blotting was performed to compare the regional protein expression of NMM-II and associated proteins including smooth muscle actin, kinesin, and E cadherin in small intestinal tissue between BNP vs. vehicle infused mice. Fluorescence microscopy revealed markedly increased localization of NMM-II at the crypts and core of intestinal villi of the jejunum, ileum and colon of BNP treated mice compared to vehicle. Transmission electron microscopy revealed that the microvilli of BNP treated mice assumed the distinctive appearance of ‘relaxed’ microvilli compared to vehicle. Such decrease in contractility was previously shown to decrease para-cellular permeability of epithelia. Our observation indicates that BNP alters the localization of NMM-II in intestinal villi and makes the intestinal villi structures assume a state of decreased permeability of the apical junctional complex. Further characterization of this process and understanding the specific mediators involved could lead to the identification of novel therapeutic targets for various disease states such as heart failure and malabsorption.